Why telomeres shorten and restoration strategies in aging

VIDEO SPONSOR - Longevity.Technology: www.longevity.technology/?utm...
Telomeres are DNA repeats found at the ends of chromosomes. They serve to maintain chromosomal stability. The caveat is that they shorten each time the cell divides due the end replication problem. That is, unless the cell expresses telomerase. Telomerase is a ribonucleoprotein complex (a complex containing protein and RNA) that can add back telomeric repeats.
So what happens if telomerase isn't expressed? Well, after ~50 divisions the shortened telomeres induce a cellular state known as replicative senescence. Basically, the cell stops dividing. This is thought to be beneficial since it acts as a tumour protective mechanism by preventing uncontrolled cells from replicating too many times. However, it can also reduce the regenerative potential of tissues.
Senescent cells accumulate with age. Moreover, a weak negative correlation is also seen between age and telomere length.
For these reasons there is much interest in using telomere restoration strategies to target aging and for treatments people suffering with telomeropathies. But how would this be achieved and would it pose a cancer risk?
In this video we will address these questions and provide the details of why telomeres shorten with age and how the length could be restored.
TIMESTAMPS
Intro - 00:00
Why telomeres shorten - 00:45
Telomerase - 03:20
Cellular senescence & Hayflick limit - 04:30
Aging link (organismal/mouse studies) - 06:00
Telomere restoration strategies - 08:15
REFERENCES
Telomeres: history, health, and hallmarks of aging - doi.org/10.1016/j.cell.2020.1...
Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells - doi.org/10.1016/j.stem.2020.0...
Jaskelioff, M., Muller, F., Paik, JH. et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 469, 102-106 (2011). doi.org/10.1038/nature09603
Longevity, Stress Response, and Cancer in Aging Telomerase-Deficient Mice - doi.org/10.1016/S0092-8674(00...
Icons in intro; "www.freepik.com/free-photos-v..."Background vector created by freepik - www.freepik.com

[@TheSheekeyScienceShow]

I think there is much still to learn about telomeres but I hope this video has given a good overview of our current understanding. p.s who doesn't love the shelterin complex!? :D

[@higreentj]

@@Freja_Solstheim Evolution is about keeping the species alive, not the individual and the main survival strategies are genetic variation and alliances between species. Research into long lived individuals (110 years) show theses genes COA1 and STK17A efficiently repair DNA damage. The SENS approach of damage repair will take us part of the way to ending aging but I think we will need a certain amount of genetic modification to completely end aging.

[@maharshipandya8221]

Thanks a lot for this video, I am a big fan of yours.

[@gamblinguru33]

Just wanted to say thanks for making these amazing videos. The longevity movement is lucky to have you on its side. I'm not sure if you saw the in vitro study of telomerase-inducing compounds, but a blend of Astragalus, Rhodiola rosea, broccoli seed extract, and vitamin D was significantly more powerful than TA-65 at increasing telomerase.

[@arqi123]

I love your anti aging videos!

[@JazenValencia]

Chinese Astragalus (cheap)is where they get (expensive) TA-65, and the Astragalus works better. The peptide Epitalon, also under the name Epithalon lengthens Telomeres. 5 to 10 mg/day for 10 to 14 days typically once a year.

[@thomasmuller1850]

Astragalus, the whole root, didn't well in self-experiments.

[@danno1800]

Great job explaining telomeres - thanks very much!

[@daveoatway6126]

Very nice description of a complex process. Best I've seen. Thank you

[@elba_magellan]

awesome vid , love the illustrations and lucid explanation

[@johnanderson9619]

Excellent presentation. Thank you.

[@CrumbleLives]

Great video! So much to think about!!

[@jshaw4484]

This is great! Thank you!

[@aclearlight]

Great work! Thank you so much for going deep...this chemist salutes you!

[@danielwikstromshemer5947]

Great video!!

[@keng7758]

I really love your videos and your deep exploration into these aging and health related discussions! Also, I like your accent as you are a joy to listen to! Thank you!

[@JenMarco]

Awesome video! I usually have to watch videos at high speed but this was perfect!

[@saraassar5264]

Very informative and easy to understand. Thanks

[@urpgag2]

3:30 telomerase Acetyl L-Caarnitine

[@rylaczero3740]

Been subscribed to your channel for some weeks. The quality and delivery of content is top notch. I am not of Molecular Biology background but interested in it since I age. The genome is a latent space representation from my perspective and might help in gaining some insights without doing actual experiments that take time.

[@TheSheekeyScienceShow]

Thank you! 😊

[@Ms.Robot.]

Awesome 💋❤️ Brilliant presentation.

[@willofdodge1]

WOW, You are so smart. I hope you go on Joe Rogan Podcast one day

[@drkmlakshmipathy]

Wonderful presentation..I have seen first of this kind ....very scientific and illustrative too..lots of regards from Chennai India

[@schuggy4408]

This understanding is the key to the real fountain of youth. We're on the verge of something very cool in the human species. We need make some real big cultural adjustments very soon, because it's about to get real-real.

[@stephanieh.4322]

What do you mean? I’m interested to learn more please.

[@brienq]

Well thank you very much! This really helps fill in a lot of mechanistic details I didn't know about. I wonder what you would think of the potential of the many additional dietary agents beyond TA-65 and Danazol showing telomerase activating effects, with even some of these, albeit a limited number, having clinical studies showing a telomere lengthening effect? Some are the nutrients/bioactives such as vitamin D, tocotrienols, beta carotene, silymarin, triterpenes, and other flavonoids (luteolin, apigenin, puerarin).

[@ThanosFrl]

wow very informative

[@JR-ht2vy]

Your videos are always interesting with lots of content. After viewing this video my question is; what will you personally do to maximize the current available to extent your longevity? Thanks!

[@themacso4157]

Your voice is soothing

[@patrickmchargue7122]

Informative, as always. Thank you.

[@kimandreblikas1762]

Hi! What program and gadget do you use to draw?

[@brewhog]

This was fantastic. I'm so glad you went into more of a deep dive than most other videos on this topic. I'm super curious about your thoughts on this so called "WILT 2.0" as Aubrey De Grey calls it (From MAIA Biotechnology). Conceptually it sounds like a molecule that kills any cells that begin to express telomerase. I've never heard anything like it before (Not sure how promising or dangerous that could be).

[@TheSheekeyScienceShow]

Thanks! And not heard of it but am intrigued

[@brewhog]

@@TheSheekeyScienceShow Check out the video with Aubrey De Grey and Richard heart (Streamed live on May 11 2021). He talks about it for a few minutes. It has its own youtube video chapter so you can skip to it.

[@Starchaser63]

Interesting

[@ScottRobb]

you might wanna look into trf1, pot1 and pot 2

[@GuidetteExpert]

So what tablets actually work?

[@susymay7831]

Does anyone have comments on the suppliment Basis, from Elysium Health?

[@rhyothemisprinceps1617]

Interesting new review article out by Saretzki et al. in Biomedicines on non-canonical functions of TERT and neurodegeneration.

[@mr.e7201]

11:00 Would you be able to make a type of telomerase that can spot the difference between healthy cells and cancer cells? Maybe do this via the therapy delivery mechanism?

[@paulwolf3302]

Any thoughts on centella asiatica or astragalus? They are traditional medicines used in China, India and Indonesia for hundreds or thousands of years, and sold as remedies for all kinds of things, including anti aging claims. See D Tsoukalas' 2019 paper, "Discovery of potent telomerase activators: Unfolding new therapeutic and anti-aging perspectives" in Molecular Medicine Reports. There have been more recent studies also, such as by AH Karsono on a centella asiatica ethanol extract. These were in vitro on human cells. They seem to be pretty safe, and as far as I can tell, neither are associated with cancer risk. I agree with a previous comment, that if cancer cells activate telomerase and can live forever, the reverse isn't necessarily true, that activating telomerase could cause cancer cells to form, or stimulate cancer cell growth. (they already activate telomerase) I guess that if your cells can live longer, they can accumulate more mutations and eventually become cancerous, but wouldn't that be true for any kind of anti aging strategy?

[@george6252]

I would like to see a podcast on Carbon 60. Increased lab rat lifespan by 90%. Been using it for 3 years in October. Plan to have a telomere blood test then.

[@rhyothemisprinceps1617]

search the channel - there's a video on it

[@petemarx1129]

Seems as only option that works.

[@RumorBreaker]

good thing i understand what atoms, molecules, cells and basic stuff. otherwise i wouldn't have understand this.

[@chrisdonner2910]

Dr. Cooke's mRNA work is incredible. "Dr. John P. Cooke is the Chair of the Department of Cardiovascular Sciences at the Houston Methodist Research Institute, Director of the Center for Cardiovascular Regeneration, and Medical Director of the RNA Therapeutics Program in the Houston Methodist DeBakey Heart and Vascular Center in Houston, Texas."

[@conjering]

Wow

[@dw4076]

What do you think of epitalon

[@TheSheekeyScienceShow]

Couldn't really find much recent data on it which makes me question the approach, so basically dont think there is enough data for me to have any opinions

[@TheSheekeyScienceShow]

Obviously, if there is more recent data that i didnt find, let me know 😊

[@dw4076]

@@TheSheekeyScienceShow thankyou for replying

[@kral3046]

First time hearing this compound, did some brief research; People on Reddit are saying it slightly darkens their hair color and has noticeable improvements on their skin and makes them have vivid dreams and be more energetic overall (All these are anectodal tho) A quick search on PubMed yields some results but almost all of them are kinda outdated: pubmed.ncbi.nlm.nih.gov/?term=epitalon

[@danno1800]

@@kral3046 thanks for the research - much appreciated.

[@pavelbaidurov228]

Cancer goes up with thymus shrinking. And If you restore Thymus - it will be ok to restore telomeres?

[@diamond_s]

Melatonin can reverse Thymus shrinking in mice. It also appears to inhibit prostate tissue growth in rats. Humans have age related drastic decline in melatonin production(which some call melatonin the clock of aging, or the conductor of the body's hormonal orchestra), this might have something to do with both thymic shrinking and prostate enlargement issues which eventually become common amongst most men at latter ages.

[@startingtoday4663]

QQQ...are the telomeres at the end of the entire DNA strand or at the end of the Chromosomes?

[@TheSheekeyScienceShow]

So there isnt just one long DNA strand, but several. Each strand has telomeres at either end in human cells

[@PravinPatil41]

I read somewhere that fasting helps. Does it?

[@petemarx1129]

@@patriotjoe3110 This is reasonable assumption.

[@blakemorgan8450]

I count myself lucky for not getting cancer from taking TA-65 5 years ago. It was cool seeing the results of my telomere tests though. I'll be a guinea pig for anything promising haha.

[@DriverJ-N]

Ta65 works? I’m gonna get some for me and my mom

[@blakemorgan8450]

@@DriverJ-N It lengthens telomeres, but whether that's good or bad remains to be seen. Could just make it easier to get cancer for all we know.

[@petemarx1129]

@@blakemorgan8450 This is simplified view on this subject.

[@Chris-kr7gg]

I am dubious about this comment and TA-65 ability to extend telomeres length.

[@blakemorgan8450]

@@Chris-kr7gg Hi Craig, I can show you photos of the test results if you'd like.

[@yavuzbahadrtaktak8020]

Chimpanzee's telomeres fused together: voila, here is a hominini!

[@kral3046]

So many unknowns, yet just look how much we know compared to 1990's. Now imagine 2050's, (Accounting for the ever-accelerating rate of technological progress over time) we will learn and uncover things we didn't know existed even more so than we have in the last 30 years and then will come 2080's and so on.. I'm really hopeful for the future and hope that everyone watching this video will get to be cured of this ultimate disease :D

[@petemarx1129]

All makes sense in case that human race doesn't destroy itself prior to 2050. What is not very unlikely.

[@michellemorgan6578]

Well said. Exactly right. Godspeed for a cure from telomere related diseases ❤🙏

[@t1relaxation]

Telomeres can't be everything about age. Why do the telomere length of some parents match that of their kids but you can still easily tell who is the parent and who is the child by appearance?

[@brienq]

Are you sure you aren't mixing up telomeres with chromosomes? Is there a study showing that kids have telomere lengths matching that of their parents? The parents telomeres should be much shorter due to cell divisions over the years that would shorten the telomere length with each subsequent division. Chromosome are what determine appearance and telomeres are not part of that except in a very indirect way.

[@bluewaters3100]

I agree in that I believe diet and supplements are only part of the anti-aging puzzle. Breathing,sleep, meditation, and activating various states of consciousness are probably more important.

[@BR-hi6yt]

Usual thing - more robust work needs to be done.

[@pavelbaidurov228]

Nice video. Pls take some drawing courses for digital art(with graphic tablet + krita/photoshop), I feel big potential, in 5 years you will be able to draw some awesome cell structures!!

[@roustamakhmetov2926]

There is a video with 83 year old doctor claiming he increased his telomeres length by 100%: kzbin.info/www/bejne/qX7XdGdmfaaYpbs What do you think about it? It lacks specific information about this test, like the exact model of the chamber, pressure, duration of the sessions, percentage of oxygen, etc. I am pretty sure you won't get the same results in inflatable chambers and perhaps some of the health clinic chamber models. It would be nice to know if this is repeatable, so let's say you your 60 sessions and get X % of telomere length increase. You wait couple of years and do another set of 60 sessions. Would you get the same result? Would it be a bit less? Would it be a lot less or is this just one off effect which is not repeatable? Also is there any research with younger people? I would assume you won't get 100% increase in length, but would it be the same in absolute increase or maybe even better? Is there a risk of getting cancer through this therapy?

[@fairworld2522]

Whil the content is good, the explanation is too fast

[@advertiserfriendlyusername5362]

They're called aglets and their true purpose is sinister.

[@sciencesimplified3890]

I dont believe telomerase activity will stimulate cancer growth and there is no causal evidence support this fear. Cancers have unregulated cell growth, and this growth requires telomerase activity. However, supporting telomerase activity has no effect on stimulating unregulated cell growth(as far as we know and there is no reason to believe otherwise, although of course anything is possible). Telomerase activity is used by cancers yes, but if you give a healthy cell with regulated cell growth telomerase, this wont suddenly trigger aberrant activation of the cell cycle, it will simply allow the cell grow uncontrollably if it already has the genetic mutations necessary for uncontrolled cell growth. Honestly, it probably is pushing a dysfunctional cell one step closer to being immortal and this is a concern and the transient idea is interesting and theoretically abrupt supplementation to TA65 should seize growth. This was a well designed video great data.. personally I feel comfortable taking TA-65 but perhaps you're right to heavily weigh safety when there are so many unknowns

[@ungoyaji2012]

Thank you for the information. I'm writing a research proposal on telomere shortening. If u got any sources or researches i should study that can help me plz let me know. Thanks again.

[@AceKinG2024]

Telomeres shortening effect on aging is overrated

[@schuggy4408]

No way

[@AceKinG2024]

@@schuggy4408 it is and I can prove it

[@schuggy4408]

@@AceKinG2024 Let's talk it out. I'm up for the debate. Let's seek our truth together. I'm open minded to what you have to say. Show me...

[@petemarx1129]

@@schuggy4408 This is how usually bold statements end up

[@IINoirII]

+

[@georgeblackmore1711]

Too boring